A locus on chromosome 1 promotes susceptibility of experimental autoimmune myocarditis and lymphocyte cell death.
We previously identified by linkage analysis a region on chromosome 1 (Eam1) that confers susceptibility to experimental autoimmune myocarditis (EAM). To evaluate the role of Eam1, we created a congenic mouse strain, carrying the susceptible Eam1 locus of A.SW on the resistant B10.S background (B10.A-Eam1 congenic) and analyzed three outcomes: 1) the incidence and severity of EAM, 2) the susceptibility of lymph node cells (LNCs) to Cy-enhanced cell death, and 3) susceptibility of lymphocytes to antigen-induced cell death. Incidence of myocarditis in B10.A-Eam1 congenic mice was comparable to A.SW mice, confirming that Eam1 plays an important role in disease development. Caspase 3, 8 and 9 activation in LNCs following Cy treatment and in CD4(+) T cells after immunization with myosin/CFA was significantly lower in A.SW than B10.S mice whereas B10.A-Eam1 congenic mice exhibited an intermediate phenotype. Our results show that Eam1 reduces lymphocyte apoptosis and increases susceptibility to EAM.
Ligons
Davinna L
DL
Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD 21205, USA.
Guler
Mehmet L
ML
Li
Haiyan S
HS
Rose
Noel R
NR
D000818:Animals; D001327:Autoimmune Diseases / Q000235:genetics* / Q000276:immunology* / Q000378:metabolism; D020169:Caspases / Q000378:metabolism; D016923:Cell Death; D033481:Chromosomes, Mammalian / Q000235:genetics*; D004789:Enzyme Activation; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D007114:Immunization; D008213:Lymphocyte Activation / Q000276:immunology; D008214:Lymphocytes / Q000166:cytology* / Q000378:metabolism*; D008297:Male; D051379:Mice; D009205:Myocarditis / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D009218:Myosins / Q000276:immunology
D020169:Caspases; D009218:Myosins